Research proposed in this application will center on three broad areas: Integration. Using the transfection technique with infectious DNA we plan to confirm our tentative evidence against tandem integration of different avian oncoviruses. We will also explore the question of whether there is a limited number of cellular integration sites which can be saturated with provirus and whether there are different types of integration sites for avian oncoviruses having different terminal genetic sequences. Loss and Acquisition of src. A collaborative investigation with Dr. Lai of this department, Dr. Varmus in San Francisco and Dr. Duesberg in Berkeley is planned to define the conditions for the loss of the src gene and to elucidate the mechanism of this deletion from the avian sarcoma virus genome. Genetic and restriction enzyme analysis, gel electrophoresis, heteroduplex mapping, src specific hybridization and oligonucleotide fingerprinting will be used in this study. A search will be continued for a system in which the acquistion of cellular src sequences by a transformation defective virus can be demonstrated reproducibly. Carcinoma and Leukemia Viruses. We have chosen avian myelocytoma virus MC29, the Murray-Begg reticuloendothelioma virus MH2, avian myeloblastosis virus and avian erythroblastosis virus as models to study leukemogenesis and induction of carcinomas. Replication defects of these viruses will be defined. Evidence for specific transforming genes will be sought and basic mechanisms of transformtion will be studied in hematopoietic and epithelial cell cultures.